ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8365T>C (p.Tyr2789His)

dbSNP: rs878853609
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000232896 SCV000283340 uncertain significance Hereditary breast ovarian cancer syndrome 2024-10-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 2789 of the BRCA2 protein (p.Tyr2789His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 236917). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004020740 SCV003903980 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-25 criteria provided, single submitter clinical testing The p.Y2789H variant (also known as c.8365T>C), located in coding exon 18 of the BRCA2 gene, results from a T to C substitution at nucleotide position 8365. The tyrosine at codon 2789 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003228916 SCV003926266 uncertain significance not provided 2022-11-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 8593T>C; This variant is associated with the following publications: (PMID: 12228710)

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